PURPOSE To define the maximum-tolerated dose (MTD) and better tolerated sequence of paclitaxel by 3-hour infusion plus bolus doxorubicin (DOX) and to evaluate antitumor efficacy. PATIENTS AND METHODS Thirty-five women with metastatic breast cancer (dominant visceral metastases in 56%, and involvement of > or = three sites in 67%) who never received chemotherapy of any type were studied. Paclitaxel every 3 weeks (125 mg/m2 starting dose) was increased by 25-mg/m2 steps in subsequent cohorts of patients. DOX (60 mg/m2 fixed dose) was administered 15 minutes before the start of or after the end of paclitaxel for a maximum of eight cycles. Subsequently, patients in continuous response could receive single-agent paclitaxel (175 to 200 mg/m2 every 3 weeks). The drug sequence was alternated in consecutive patients and in the first two cycles. RESULTS Severe neutropenia that lasted greater than 7 days (n = 4), febrile neutropenia (n = 7) and grade III oral mucositis (n = 6) defined the MTD of paclitaxel at 200 mg/m2 in 34 assessable patients. Grade II peripheral neuropathy occurred in 33% of patients. Six women (18%) developed clinically reversible congestive heart failure (CHF) after a median of 480 mg/m2 total DOX. Drug sequence had no effect on toxicities. High efficacy on all metastatic sites in 32 assessable patients accounted for a 41% complete response (CR) rate (95% confidence interval [CI], 24% to 59%) and 94% overall-response rate (95% CI, 79% to 99%). After a median follow-up of 12 months (range 3 to 18), the median response duration is 8 months (range, 2+ to 18+) for complete responders and 11 months (range 1+ to 15+) for partial responders. CONCLUSION The rate of CR and incidence of CHF may be an expression of therapeutic and toxic enhancement due to the schedule used in this trial. Until clarification of this possibility, this promising combination should be used in investigational trials.

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An increasing number of cancer patients live longer, and palliative care has become an important part of their treatment. Symptoms are often inadequately assessed and managed. A significant challenge in clinical trials is to control for the variability of the samples being studied. To overcome this problem, classification systems have been developed in order to characterise and stratify patients by grouping them according to major common characteristics. The lack of agreed methods for the assessment and classification of cancer pain has been clearly indicated in clinical trials and in clinical practice and may be one possible explanation for the inadequate treatment of cancer pain. This was the background to an international expert meeting arranged in September 2009 in Milan, Italy. The primary aims were to produce recommendations on how to assess and classify cancer pain and to recommend a strategy for the further development, validation and implementation of an international cancer pain classification and assessment system. The recommendations consisted of two basic working proposals, nine specific working proposals and seven recommendations for the further development of a cancer pain classification system. Examples of specific working proposals were to include pain intensity, pain mechanism, breakthrough pain and psychological distress as the core domains in this classification of cancer pain and to measure pain intensity with a 0-10 numerical rating scale with 'no pain' and 'pain as bad as you can imagine' as anchors. The proposed name for this international standard is Cancer Pain Assessment and Classification System (CPACS).

Gastrointestinal obstruction is a common problem in advanced malignant disease, but its management remains controversial. In those patients for whom surgery is not appropriate, medical intervention is the only remaining option. We present a series of 14 patients with intestinal obstruction who were managed with subcutaneous injections of octreotide, a somatostatin analogue which reduces the volume of gastrointestinal secretions. Good control of vomiting was achieved in 12 patients, and no major side effects were observed. Octreotide would appear to be a useful drug in this clinical situation.

The aim of the study was to assess vomit and pain control in terminal cancer patients with inoperable gastrointestinal obstruction, using a pharmacologic symptomatic treatment which prevents recourse to nasogastric tube placement and intravenous hydration, in hospital and home care settings. Twenty-two symptomatic patients, who were judged as inoperable, were treated with a pharmacologic association of morphine hydrochloride and scopolamine butylbromide as analgesics and haloperidol as an antiemetic. The drugs were administered by continuous subcutaneous infusion via a syringe driver or intravenously only when a central venous catheter had been inserted previously. Daily recordings included assessment of pain, number of vomiting episodes, dry mouth, drowsiness, and thirst sensation. Data were examined before starting the treatment (T0), 2 days after (T2) and 2 days before death (T-2). They showed that there was a significant decrease in the pain score (p less than 0.001) on T2 and a further decrease on T-2 (p less than 0.05). Vomiting was controlled in all patients, with the exception of three patients with upper abdomen obstruction who required nasogastric tube placement. Dry mouth showed an upward trend throughout the observation period (p less than 0.05) but was successfully treated by administering liquids by mouth or ice-cubes to suck. Drowsiness too presented an upward trend from T0 to T-2 (p less than 0.001). Only one patient out of 16 who reported to be thirsty required intravenous hydration. We believe that in terminal cancer patients, vomit and pain resulting from inoperable intestinal obstruction, with the exception of obstruction of the upper abdomen, can be controlled through administration of analgesic and antiemetic drugs, in the hospital and at home, without recourse to nasogastric tube placement or intravenous hydration.

According to the data of the literature, the prevalence of pain in cancer patients at various stages of the disease and the settings of care range from 38 to 51%, with an increase of up to 74% in the advanced and terminal stages. Despite published World Health Organization (WHO) guidelines for pain management, 42 to 51% of cancer patients receive inadequate analgesia and 30% receive no analgesics at all. A 3-year Research Project "Towards a Pain-free Hospital", which began one year ago, is ongoing at the National Cancer Institute of Milan. The research is organized in three subsequent steps. In the 1st one, a series of patient- and staff-oriented evaluation tools are used to assess the level of appropriateness of pain communication, assessment, management and control of the in-patients. The 2nd step will implement a number of continuing educational interventions aimed at improving patient awareness and staff knowledge of the appropriate pain assessment and management in order to respond to the patient's pain problem. In the 3rd step, all the assessment tools used in step one will be applied again to establish the prevalence of pain, the causes and intensity and patient satisfaction with pain management and to evaluate the impact of the interventions performed during the 2nd step regarding the overall ability of our hospital to tackle pain emergency in the hospitalized cancer population. The results relative to the 1st step are herein reported, in particular as regards the study on prevalence, causes, severity of pain, the interference of pain with sleep, mood and concentration, the use of pain medications and the relief obtained, the structural validity and internal consistency of the assessment tool used. A total of 258 patients hospitalized for at least 24 h were interviewed by 9 physicians using a brief structured questionnaire prepared ad hoc: 51.5% of the patients presented pain during the previous 24 h caused by surgery (49.6%) or by the tumor mass itself (29.3%). Out of the 133 patients with pain, a high degree (much or very much) of pain at rest was present in 27.1% and pain on movement in 30.8%; 31.6% did not take any analgesic treatment, and 14.3% of the latter reported a high degree of pain at rest and 21.4% on movement. Pain interfered with sleep from much to very much in 28.8% and with irritability and nervousness in 15.9% of the patients. In the 91 patients taking analgesics, 57.2% reported a high degree of pain relief. A high degree of pain and interference, however, was associated with low relief levels. The assessment tool used was shown to have a good structural validity and internal consistency (Chrombach alpha index of interference scale = 0.73). Although the Milan Cancer Institute has the longest tradition in Italy of pain assessment by means of validated tools and pain management according to the WHO guidelines and educational efforts in this field, the results of the study clearly show that it is necessary to persevere with continuing educational and informative programs in order to reduce ...

The moral imperative to adequately manage pain is being increasingly recognized worldwide. A comprehensive pain management approach that addresses the various presentations of pain in patients with cancer is required, including appropriate management of breakthrough pain. Breakthrough pain commonly occurs in patients with advanced cancer and is disabling to the individual and burdensome to society, yet it is often inadequately managed. Because pain is heterogeneous, the best management of an individual's pain, including breakthrough pain in cancer, requires a thorough assessment to tailor the treatment strategies. Recently developed guidelines support this approach and recommend treating breakthrough pain using rapid- or short-acting opioids with pharmacodynamics that mirror the rapid onset and short duration of the presenting pain. This approach should be part of a comprehensive strategy to treat pain within the context of the primary disease trajectory, offering continuity of care and access to specialized palliative care when appropriate.

Evidence to support an analgesic role for bisphosphonates and denosumab is weak. Bisphosphonates and denosumab appear to be beneficial in preventing pain by delaying the onset of bone pain rather than by producing an analgesic effect per se.